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- W2485942948 abstract "Background: Sotrastaurin (STN), a novel oral protein kinase C inhibitor, blocks early T-cell activation. Its immunosuppressive effect was assessed in a non-human primate (NHP) model of kidney transplantation (Tx). Methods: Cynomolgus monkeys received life-supporting kidney allografts and daily oral treatments with STN or cyclosporine A (CsA) alone or in combination.Results: STN alone at 50 mg/kg QD prolonged graft survival up to predefined end point of 29 days (n=2). When STN was given at 25 mg/kg BID, median survival time (MST) of grafts was 27 days (n=4). STN or CsA monotherapy (both at 20 mg/kg/day) did not increase MST (6 and 7 days, with n=2 and 5, respectively), whereas when given as combination (20/20 mg/kg/d) prolonged MST by >100 days (n=5). The MSTs for STN/CsA combinations at 7/20 and 2/20 mg/kg/day were >100 days (n=3) and 22 days (n=2), respectively. In all of these combination groups, the STN trough levels (C0) were dose-related (30–182, 7–41 and 3–5 ng/mL, respectively), while the CsA-C0 levels remained unchanged, suggesting that the potentiation of CsA efficacy by STN was not due to PK interactions. This was confirmed by separate PK studies in normal NHP.Conclusion: STN appears to be an efficacious immunosuppressive agent for the prevention of organ rejection in NHP. This supports its current development in clinical transplantation." @default.
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- W2485942948 date "2012-01-27" @default.
- W2485942948 modified "2023-09-27" @default.
- W2485942948 title "SOTRASTAURIN, (AEB071), PROLONGS KIDNEY ALLOGRAFT SURVIVAL ALONE OR IN COMBINATION WITH CYCLOSPORINE IN NON-HUMAN PRIMATES" @default.
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